Naturally-occurring protease inhibitors, (leupeptin and antipain obtained from Actinomycetes) are used to test the role of protease in gastrointestinal carcinogenesis such as MNNG for gastric cancer, azoxymethane for colon cancer, and diisopropanolnitrosamine for pancreatic cancer. Further studies on the role of protease on metastasis of ascites hepatoma cells is being carried on. Results show that leupeptin decreased metastasis of AH 7974 cells in the lungs of Donryu rats.